The present invention relates generally to wound healing polymeric networks, matrices, or gels, to compositions and compounds to form wound healing polymeric networks, to methods of synthesizing wound healing polymeric networks and to methods of treating wounds using wound healing polymeric networks.
The following information is provided to assist the reader to understand the invention disclosed below and the environment in which it will typically be used. The terms used herein are not intended to be limited to any particular narrow interpretation unless clearly stated otherwise in this document. References set forth herein may facilitate understanding of the present invention or the background of the present invention. The disclosure of all references cited herein are incorporated by reference.
Wound healing is a dynamic and orchestrated process that involves cellular and matrix components acting together to re-establish the lost tissues. Co-morbid physiological and psychological conditions and aging compromise this healing, which can be ameliorated by modulating these underlying conditions (with the exception of aging). Infections adversely impact wound repair through ongoing chronic inflammation and production of toxic molecules and metabolites from both the microbe and the immune response. Skin wounds are particularly prone to these infections as they are both exposed to pathogens and also harbor commensural microbes that can infect compromised tissue. Thus microbial proliferation must be controlled or prevented to enable proper healing.
The existence of a variety of wound types with varied healing modes and phases has led to the development of different types of wound healing matrices in attempts to improve upon physiological healing. Traditional wound management involves disinfection and provision of a moist environment to encourage the establishment of the best environment for the natural healing process. The use of biological sealants has been promoted primarily based on their ability to enhance coagulation in addition to their capacity to create a mechanical barrier at the site of bleeding.
In designing a material or matrix to promote wound healing, one that is capable of providing adequate antimicrobial activity is desired provided that the antimicrobial substance(s) present in the matrix do not compromise the physiologic healing, including hemostasis and immune functioning and the repair-promoting physiochemical aspects of the matrix. To be beneficial, the antimicrobial agent preferably exerts its effect over the relevant time scale of days, without being washed out by tissue fluid flows or neutralized by serum- and tissue-derived factors and enzymatic activities.
With the surge of antibiotic resistance, impregnating a matrix with a necessarily broad-spectrum antibiotic is becoming a concern. Moreover, complex molecules may form complexes with the surface of polymer and modify it further resulting in confounding diffusion and elution calculations. This also may produce novel immunological epitopes that would be recognized by the body as foreign.
Silver is a widely used nonspecific antimicrobial, as it acts against a very broad spectrum of bacterial, yeast and fungal species likely to contaminate wounds and body cavities. See, for example, Thomas S, McCubbin P. A comparison of the antimicrobial effects of four silver-containing dressings on three organisms. J Wound Care 2003; 12(3):101-7. This action derives from the binding of the positive silver ions with the negatively charged microbial proteins preventing their replication, and via attachment to sulfhydryl groups, preventing their respiration and resulting in inhibiting their proliferation. See, for example, Holt K B, Bard A J. Interaction of silver(I) ions with the respiratory chain of Escherichia coli: an electrochemical and scanning electrochemical microscopy study of the antimicrobial mechanism of micromolar Ag+. Biochemistry 2005; 44(39):13214-23; Bragg P D, Rainnie D J. The effect of silver ions on the respiratory chain of E. coli. Can J Microbiol 1974; 20(6):883-9; and Darouiche R O. Anti-infective efficacy of silver-coated medical prostheses. Clin Infect Dis 1999; 29(6):1371-7. Silver also works on biofilms, a critical challenge for embedded foreign bodies. See, for example, Chaw K C, Manimaran M, Tay F E. Role of silver ions in destabilization of intermolecular adhesion forces measured by atomic force microscopy in staphylococcus epidermidis biofilms. Antimicrob Agents Chemother 2005; 49(12):4853-9.
Currently available products for facilitation of wound healing have met with only limited success. It thus remains desirable to develop wound healing polymeric networks, compounds for forming such wound healing polymeric networks, methods of synthesizing or forming such wound healing polymeric networks and methods of treating wounds using such wound healing polymeric networks.